The purpose of this study is to characterize the physiological and biochemical properties of the viral polypeptide designated ICP4 which is synthesized soon after infection of human cells by herpes simplex virus. Previous work by others suggests that ICP4 functions as a regulatory protein to control the expression of several viral genes necessary for virus production in infected cells. ICP4 will be purified from extracts of HSV infected cells using conventional column chromatographic techniques. Column fractions will be assayed by polyacrylamide gel electrophoresis and by reaction with antibody to ICP4. The size and composition of the native protein will be determined. Affinity for DNA will be measured, and the location and sequence of DNA-binding sites on HSV DNA will be investigated. The effect of ICP4 on the pattern of transcription of HSV DNA will be examined using recently developed in vitro transcription systems, in collaboration with other investigators.